MM25: A phase 1b/II study of the efficacy of Venetoclax, Iberdomide and Dexamethasone (IberVenD) for patients in first or second relapse of Multiple Myeloma with t(11;14)

This is an adverse event-adaptive trial design for safety purposes. There will be intra-patient dose escalation over the first three cycles, i.e. all patients will start at ‘combination level 1’ during cycle 1, if there is no treatment-related Grade 3 neutropenia or Grade 4 thrombocytopenia, as per Common terminology criteria for adverse events version 6 (CTCAE v6), dose will be escalated to ‘combination level 2’ during cycle 2, then ‘combination level 3’ during cycle 3, respectively: • Cycle 1 (combination level 1)*: Iberdomide 1.3mg + Venetoclax 200mg • Cycle 2 (combination level 2): Iberdomide 1.3mg + Venetoclax 400mg • Cycle 3 onwards (combination level 3): Iberdomide 1.6mg + Venetoclax 400mg All patients will receive dexamethasone in each treatment combination level. *Note: In case of treatment related Grade 3 neutropenia or Grade 4 thrombocytopenia at ‘combination level 1’, then the dosing level will be deescalated to ‘combination level -1’: Iberdomide 1.0mg + Venetoclax 200mg. Dosing will be done on a 28-day cycle: - Venetoclax given orally from days 1-28 -Iberdomide given orally from days 1-21 -Dexamethasone given orally, 40mgs weekly (20mg for patients >75 years of age) Participants will continue on treatment until one of the following criteria applies: • Disease progression • Intercurrent illness that prevents further administration of treatment • Unacceptable AE(s) • Patient decides to withdraw from treatment or the study, or • General or specific changes in the patient's condition render the patient unacceptable for further treatment in the opinion of the investigator. Compliance will be monitored via drug accountability exercises completed by the participating site and the sponsor.